Expression Of Myeloid-associated Antigens Research Articles

Clinical manifestations and diagnosis of acute myeloid leukemia in a patient with a medical history of pulmonary tuberculosis (a case report)

The aim is to familiarize practitioners with the initial clinical manifestations of acute myeloid leukemia and its diagnosis in a patient with a past medical history of pulmonary tuberculosis.Materials and methods. The article presents a clinical case of acute myeloid leukemia clinical manifestations based on our own clinical experience and its diagnosis in the patient with previous pulmonary tuberculosis. The patient was followed-up and diagnosed with acute myeloid leukemia in the Municipal Institution “Zaporizhzhia Regional Tuberculosis Clinical Dispensary”.Results. The patient presented in this study was diagnosed with pulmonary tuberculosis and received antimycobacterial treatment including isoniazid and rifampicin, which may have initially contributed to the hematopoietic mechanisms impairment. Perhaps the stressful situation triggered the development of acute myeloid leukemia due to underlying impaired mechanisms of hematopoiesis that had occurred. In this case, the initial clinical manifestations were weakness, loss of appetite and weight loss. A clinical blood analysis with leukogram and the bone marrow biopsy with aspirate examination became priority methods in diagnosing acute myeloid leukemia. The clinical case presented primarily demonstrates patient’s irresponsibility for their own health, who having symptoms such as weakness, loss of appetite, and weight loss for 5 months as well as past medical history of tuberculosis, did not seek medical advice timely.Conclusions. In a patient with a past medical history of pulmonary tuberculosis, priority task is to confirm or rule out reactivation tuberculosis. The initial clinical manifestations of acute myeloid leukemia are: unprovoked weakness for several months; increasing exertional dyspnea; anemia, leukopenia, neutropenia, ESR acceleration. The primary methods to diagnose acute myeloid leukemia are: clinical blood test with leukogram, biochemical blood tests to determine the levels of erythropoietin, ferritin and vitamin B12; bone marrow biopsy with aspirate examination (myelogram); cytochemical examination of bone marrow (myeloperoxidase); bone marrow immunophenotyping (expression of myeloid-associated antigens).

Clinical importance of myeloid antigen expression in Moroccan patients with adult B-lineage acute lymphoblastic leukemia.

The prognostic significance of myeloid antigen (MyAg) expression in acute lymphoblastic leukemias (ALL), especially in adult patients, is still controversial. In the present report, frequency and clinical significance of MyAg (CD13 and/or CD33) in blast cells were assessed in 80 consecutive adult (≥18 years) patients with B-lineage acute lymphoblastic leukemia (B-ALL), representing 66.7% of 120 patients diagnosed as having ALL during the study period. Immunophenotyping was used to classify leukemic cells as Bor Tlymphoblasts and to identify the aberrant expression of myeloid-associated antigens. MyAg expression was documented in 52.5% of the 80 B-ALL cases analyzed. CD13 was the most commonly antigen expressed (36.3%) followed by CD33 (28.8%). No significant associations were found between the expression of MyAg and the presence of known adverse prognostic features (eg: age>30 years, male gender, high WBC count and Philadelphia positivity). Also, we failed to observe any statistically significant difference between MyAg-positive and MyAg-negative patients in terms of achievement of complete remission and overall survival at 3 years. This study demonstrates that the presence of MyAg on lymphoblastic cells lacks prognostic value In Moroccan patients with adult B-ALL.

Adult Precursor T-Lymphoblastic Leukemia/Lymphoma with Myeloid-Associated Antigen Expression Is Associated with a Lower Complete Remission Rate following Induction Chemotherapy

Prognostic studies of T-cell lymphoblastic leukemia/lymphoma (T-ALL) have been performed in small patient cohorts with conflicting results. We systematically reviewed 67 adult T-ALL patients diagnosed and treated at our institute to identify clinical and pathologic prognostic factors. The median initial WBC was 21.3 × 10⁹/l. Blasts expressed at least one myeloid-associated antigen in 33%. Karyotypes were abnormal in 32% of the cases. Fifty-six of 64 patients (88%) achieved complete remission (CR). In univariate analysis, age, gender, initial WBC, CD10, CD34 and abnormal karyotype did not predict CR. Patients expressing at least one myeloid-associated antigen had a CR of 74% compared to 94% (p = 0.04) for those not expressing myeloid antigens. None of the above factors affected relapse-free or overall survival in this cohort. Our study indicates that expression of myeloid-associated antigens is associated with a lower CR rate in adult T-ALL and may be considered in risk stratification for induction chemotherapy.

Myeloid-Associated Antigen Expression Is an Adverse Factor for Complete Remission Following Induction Chemotherapy of Adult Precursor T-Lymphoblastic Leukemia/Lymphoma (T-ALL).

We retrospectively reviewed our experience of 63 adult T-ALL patients to identify clinical and pathologic prognostic factors and build a risk-stratification model for induction chemotherapy. At presentation, the patients' median age was 30, 49 were male and 14 female, 69% had lymphadenopathy, 38% a mediastinal mass, 24% CNS involvement and 21% splenomegaly. The median initial WBC was 17.9 x 109/L (range 0.10–510.0). Blasts expressed CD34 in 42% of cases, CD10 in 33% and at least one myeloid-associated antigen (CD13 or CD33) in 27%. Karyotypes were abnormal in 34% of cases. Fifty-three of 61 patients (87%) who underwent induction chemotherapy achieved complete remission (CR) on protocols including vinca alkaloids, anthracyclines and corticosteroids. On univariate analysis; age, gender, initial WBC, CD10, CD34 and abnormal karyotype did not predict CR but patients expressing at least one myeloid-associated antigen had a CR of 71% compared to 93% (P=0.03) for patients not expressing myeloid antigens. The median follow-up was 19.2 months (95% CI: 0.1–172.8). Twenty-three patients relapsed with a median relapse-free survival (RFS) of 41.6 months (95%CI: 21.6–55.9). The RFS was longer for patients with an initial WBC of 3–50 x 109 and for cases expressing CD10 but neither was statistically significant (P=0.19, P=0.14). On follow-up, 34 patients died with a median overall survival (OS) of 31.3 months (95%CI: 16.8–56.8). Patients with CD10 expression had a longer median OS at 44.7 months (versus 19.2 months for CD10 negative patients) but again, the difference was not statistically significant (P=0.11). Age, gender, CD34, myeloid-associated antigen expression and karyotype did not influence RFS or OS. Our study indicates that expression of myeloid-associated antigens is an adverse prognostic factor for complete remission of adult T-ALL and should be considered for induction chemotherapy risk-stratification.

Pre-Pre-B Acute Lymphoblastic Leukemia: High Frequency of Alternatively Spliced ALL1-AF4 Transcripts and Absence of Minimal Residual Disease During Complete Remission

We used the polymerase chain reaction (PCR) to detect ALL1-AF4 rearrangements, the molecular hallmark of t(4;11) in a series of 46 pre-pre-B (CD19+, CD24+, CD10/CD20/cylgM/sIgM-) acute lymphoblastic leukemias (ALL). Eighteen patients (39%) exhibited fusion transcripts including 4 of 12 children and 14 of 34 adults. This genetic defect was associated with hyperleukocytosis (median leukocyte count 176 x 10(9)/L) and expression of myeloid-associated antigens (CDw65+). In contrast, only two patients from a group of 67 common (CD19/CD10+, cylgM/sIgM-) and pre-B ALLs (CD19/cylgM+, CD10 +/-, sIgM-) showed ALL1-AF4 mRNA. All PCR-positive cases showed multiple amplification products representing alternative splicing events. Moreover, reciprocal der (4)-derived AF4-ALL1 transcripts were observed in 65% of the cases analyzed. Eight of the 18 pre-pre-B ALL patients with an ALL1-AF4 recombination are currently in complete continuous remission for up to 54 months (median, 26 months). Twelve remission samples were available from seven cases, and all of them lacked evidence of minimal residual disease. Overall this study documents a similarly high incidence of ALL1-AF4 recombinations in children (infants excluded) and adults with pre-pre-B ALL and demonstrates the decline of the leukemic cell clone below the detection level of PCR in a remarkable proportion of patients under intense treatment protocols.

Ultrastructural myeloperoxidase activity and expression of myeloid-associated antigens in acute lymphoblastic leukemia

Ultrastructural myeloperoxidase (MPO) activity and myeloid-associated antigen (MyAg) expression were investigated in 12 adult patients with acute lymphoblastic leukemia (ALL). Ultrastructural MPO was detected by 3 different methods. Immunophenotyping was performed by flow cytometry, using a series of monoclonal antibodies. Ultrastructural MPO-positive blast cells were detected in 6 patients (50%). In 5 of these 6 patients, the methods detecting both MPO and platelet peroxidase (PPO) activities found MPO-positive blast cells more frequently than those detecting MPO activity alone. In 2 patients (17%), at least one kind of MyAg was positive. Ultrastructural MPO activity was detected more frequently than MyAg expression in ALL patients. This method of detecting PPO and MPO is recommended for detection of ultrastructural MPO-positive ALL.

Expression of myeloid-associated and lymphoid-associated cell-surface antigens in acute myeloid leukemia of childhood: a Pediatric Oncology Group study.

Although the expression of both myeloid- and lymphoid-associated cell-surface antigens in acute myeloid leukemia (AML) has been described, the clinical significance of such antigen expression remains unknown in the pediatric population. We sought to define an antibody panel for optimal diagnostic antigenic analysis and to test associations among antigen expression and a number of clinical features at presentation and prognosis in pediatric AML. We reviewed the extensive immunophenotypic analysis performed at the time of diagnosis on 132 assessable patients registered on a single Pediatric Oncology Group AML protocol between 1984 and 1988. Eighty-eight percent of patients were identified by testing for expression of CD33 and CD13. Overall, 61% of patients expressed at least one lymphoid-associated antigen, most commonly CD4, CD7, or CD19. Expression of CD5, CD10, CD20, or CD22, commonly detected in T- or B-lineage pediatric acute lymphoid leukemia (ALL), was uncommon; coexpression of multiple lymphoid-associated antigens was also uncommon. Expression of the monocyte-associated antigen CD14 correlated with French-American-British (FAB) M4 or M5 morphology. Otherwise, no correlation between antigen expression and FAB classification was noted. None of the myeloid, lymphoid, natural-killer (NK), or progenitor-associated antigens were associated with significant differences in the likelihood of remission induction or event-free survival when expressor versus nonexpressor groups were compared. The distribution of cell-surface antigen expression in pediatric acute leukemia usually permitted the discrimination of AML from ALL by using a limited panel of antibodies. Although the expression of lymphoid-associated antigens was common, such expression did not seem to be associated with an adverse prognosis in pediatric AML.

Myeloid-associated antigen expression lacks prognostic value in childhood acute lymphoblastic leukemia treated with intensive multiagent chemotherapy

Frequency and clinical significance of myeloid-associated antigen expression in blast cells were assessed in 372 consecutive children with acute lymphoblastic leukemia (ALL). A comprehensive panel of myeloid monoclonal antibodies representing seven cluster groups showed myeloid-associated antigen expression in 61 cases (16.4%), 18 of which expressed two or more antigens. The antigens expressed comprised CD11b (8.9% of the total series), CD13 (6.5%), CD33 (3.2%), CD36 (1.9%), CD15 (1.6%), CD14 (1.3%), and CDw12 (1.1%). No significant associations were found between myeloid-associated antigen expression and the presence of known adverse prognostic features (eg, higher leukocyte count, nonwhite race, older age). Myeloid-associated antigen expression had no effect on remission induction or event-free survival for the 267 children who had been treated with the same combination of chemotherapeutic agents (P = .34). Thus, blast cell expression of myeloid-associated antigens in childhood ALL appears to lack prognostic value in the context of contemporary intensive chemotherapy.

Myeloid-Associated Antigen Expression Lacks Prognostic Value in Childhood Acute Lymphoblastic Leukemia Treated With Intensive Multiagent Chemotherapy

Abstract Frequency and clinical significance of myeloid-associated antigen expression in blast cells were assessed in 372 consecutive children with acute lymphoblastic leukemia (ALL). A comprehensive panel of myeloid monoclonal antibodies representing seven cluster groups showed myeloid-associated antigen expression in 61 cases (16.4%), 18 of which expressed two or more antigens. The antigens expressed comprised CD11b (8.9% of the total series), CD13 (6.5%), CD33 (3.2%), CD36 (1.9%), CD15 (1.6%), CD14 (1.3%), and CDw12 (1.1%). No significant associations were found between myeloid-associated antigen expression and the presence of known adverse prognostic features (eg, higher leukocyte count, nonwhite race, older age). Myeloid-associated antigen expression had no effect on remission induction or event-free survival for the 267 children who had been treated with the same combination of chemotherapeutic agents (P = .34). Thus, blast cell expression of myeloid-associated antigens in childhood ALL appears to lack prognostic value in the context of contemporary intensive chemotherapy.

Multilineage cell involvement in Ph 1-negative, bcr-negative chronic myeloid leukemia

We report a case of Ph 1-negative, bcr-negative CML-BC, in which the primary leukemic cells displayed T-related antigens (CD7, CD4) in addition to HLA-DR and CD25 determinants. No B-lymphoid, myeloid and megakaryoblastic surface antigens were detected. In spite of this phenotype, DNA analysis revealed a germ-line configuration of the T-cell receptor β chain gene region. Moreover, in-vitro culture studies demonstrated a proliferative response of the blast cell population to natural and recombinant myeloid-related factors, while no proliferative signal was observed in the presence of IL-2. The myeloid lineage was further demonstrated by the expression of myeloid-associated antigens on cultured blast cells, which still retained the CD7 antigen. Finally, cytogenetic analysis revealed a monosomy 7 which is usually associated with a stem cell leukemia. These results support the hypothesis that Ph 1-negative, bcr-negative CML is characterized by the involvement of a multipotent stem cell capable of multilineage expression and indicate that differentiative and proliferative assays provide a further tool towards a more precise recognition of hematological disorders of uncertain origin.

Expression of Normal Myeloid-Associated Antigens by Acute Leukemia Cells

Monoclonal antibodies that react with hematopoietic cells and their precursors in a stage and lineage restricted fashion were used in indirect immunofluorescence assays to examine leukemic cells from 105 pediatric age patients. The differentiative states of blasts from 42 patients with acute nonlymphocytic leukemia (ANLL) were defined by these antibodies. When these were compared to their morphologic and histochemical levels of differentiation as defined by the French-American-British (FAB) classification, no direct relationship was found. The reactivity of these antibodies with leukemic cells from 63 patients with acute lymphocytic leukemiA (ALL) was also investigated, and the usefulness of these antibodies in distinguishing leukemias of myeloid from those of lymphoid origin was demonstrated.

Expression of normal myeloid-associated antigens by acute leukemia cells

Monoclonal antibodies that react with hematopoietic cells and their precursors in a stage and lineage restricted fashion were used in indirect immunofluorescence assays to examine leukemic cells from 105 pediatric age patients. The differentiative states of blasts from 42 patients with acute nonlymphocytic leukemia (ANLL) were defined by these antibodies. When these were compared to their morphologic and histochemical levels of differentiation as defined by the French- American-British (FAB) classification, no direct relationship was found. The reactivity of these antibodies with leukemic cells from 63 patients with acute lymphocytic leukemiA (ALL) was also investigated, and the usefulness of these antibodies in distinguishing leukemias of myeloid from those of lymphoid origin was demonstrated.